Research on the "genetics of the rotaviruses" will focus on two main areas: 1) Genetic analysis--A large number of temperature-sensitive (ts) mutants will be isolated from the model rotaviruses SA11 and NCDV. The ts mutants will be placed into genetic groups by complementation and recombination tests. The physiological properties and the various mutant groups will be examined, with specific emphasis on the synthesis and control of single-stranded and double-stranded RNA, polypeptides, morphogenesis and virion transcriptase. Recombinants segregating the genome segments of the parents will be isolated from crosses of ts mutants of SA11 and NCDV. The segregation patterns of the genome segments in these recombinants will be used to map ts lesions to specific genome segments and establish a map of genes encoding identical function in the two viruses. The polypeptides synthesized by the recombinants will be examined to establish the coding relationships between specific polypeptide species and specific genome segments. 2) Analysis of rotavirus biological properties and pathogenesis--Recombinants segregating the genes of SA11 and NCDV will be used to establish the genes encoding the viral neutralization antigen and the viral hemagglutinin. The virulence of the gastroenteritis produced by SA11 and NCDV will be examined in the mouse model system and the gene(s) encoding virulence factors will be identified using recombinants segregating the genes of SA11 and NCDV. Neurotropism of SA11 and NCDV in the mouse will be investigated and the gene(s) encoding the neurotropic character identified by analyzing the neurotropism of recombinants segregating the genes of the two viruses.